Alzheimer's Disease is a progressive disease of the human central nervous system. It is manifested by dementia, typically in the elderly, and symptoms include disorientation, loss of memory, difficulty with language, calculation, or visual-spatial skills, and by psychiatric manifestations. Alzheimer's Disease is associated with degenerating neurons in several regions of the brain. The neuropathology of Alzheimer's Disease is characterized by the presence of amyloid plaques, neurofibrillary tangles, synaptic loss and selective neuronal cell death. Amyloid plaques result from abnormal levels of extracellular amyloid beta peptide, while neurofibrillary tangles are associated with the presence of intracellular hyperphosphorylated tau protein. Symptoms typically first manifest clinically with a decline in memory followed by deterioration in other cognitive functions, and by abnormal behavior. Approximately 24 million people worldwide have dementia, of which the majority (˜60%) is due to Alzheimer's Disease (Ferri C. P. et al. (2005) Lancet 366(9503):2112-2117). More than 5 million Americans are estimated to have Alzheimer's Disease, and it is projected that this number will increase to 14.3 million by mid-century, representing a 350 percent increase from 2000. The increasing number of dementia patients in the developed world will place an enormous burden on society and the health care system.
Early diagnosis is an essential step in the treatment of Alzheimer's Disease, as early diagnosis allows subjects to receive drugs that may slow disease progression. Alzheimer's Disease is currently diagnosed using a combination of clinical criteria, which may include a neurological exam, mental status tests, and brain imaging. A diagnosis of Alzheimer's Disease is often made by eliminating other dementias. Based on these criteria, an accurate diagnosis can be difficult, especially for patients having mild or early-stage Alzheimer's Disease. An unambiguous diagnosis may be made by examining the pathology of brain tissue, but this is only feasible posthumously. Accordingly, a need exists for markers that are indicative of Alzheimer's Disease which may be used in diagnostic applications.